The main objective of this program project is to evaluate the relationship between changes in membrane structure and function and aging. In our first program project grant interesting and important alterations in membrane functions as the animal ages were noted. We wish to pursue, extend and introduce new approaches to our study of membrane alteration and aging. The projects are divided into two general categories. Those on the cardiovascular system and those of the central nervous system (CNS). There will also be studies performed on the kidney and salivary gland. Projects on the cardiovascular system involve: 1) characterization of electrophysiological, ionic and mechanical responses of cardia muscle under stress (hypoxia) and its response to drugs as a function of age: 2) characterization of hemodynamics, autonomic nervous system activity and the membranes of the vasculature. Hemodynamic considereations are included to determine whether such changes may explain or contribute to changes in cardiac, CNS and vasculature membrane alterations; 3) ionic fluxes changed during aging and Na ion plun K ion activated ATPase may be involved in these changes. Characterization of the activity of this enzyme will be conducted not only in the heart but brain and kidney. Kedney pathology suggests possible alteration in Na ion plus K ion ATPase activitity; 4) the heart will be studied also by inducing necrosis and myopathies by isoproterenol eo evaluate capacity of yound and older animals to respond to stress. Projects on the CNS will involve principally the adenyl cyclase system. 1. Cylic AMP decreases with age and the means by which this is accomplished will be studied. Cortical activity measurements will be used to determine physiological consequences. 2. Senstivity studies of the adenyl cyclase cyclic AMP will be performed to determine whether under denervation or reduced neural input compensation for this is achieved in young and older animals to different degrees. Salivary and hear adenyl cylase will be studies also. We anticipate by studying similar enzymes in different systems and inducing in the preparations 'stress' that further insight into the nature and role of membrane changes as the animal ages will be achieved.